Abstract Recent efforts to prevent healthcare-associated infections have led to increased use of disinfectants and cleaning agents. Studies suggest that occupational groups with regular exposure to these agents (e.g., health care workers) are at increased risk of asthma. However, the actual role of these common agents on the development and clinical course of asthma, and the specific agents and tasks involved, is largely unknown. The overall aim of the proposed project is to address this information gap in the Nurses' Health Study II, an ongoing prospective cohort study of 116,678 registered nurses, aged 24-44 years at baseline in 1989. Over the first 22 years, we anticipate ~6,500 incident cases of doctor-diagnosed asthma among ~10,000 nurses with a lifetime history of asthma. In 2009 and 2011, we asked all nurses about their job types and self-reported exposure to disinfectant or cleaning agents (~35% of nurses were exposed weekly). We propose to enhance assessment of both the exposure and outcome through supplementary questionnaires. All nurses with asthma will be sent questionnaires with validated questions on occupational exposures and asthma control (as defined by the 2007 NIH guidelines). The supplementary occupational questionnaire also will be also sent to a random sample of nurses without asthma (~10,000); exposure data from this non-asthmatic group will be used to create job exposure matrices (JEM) and task exposure matrices (TEM) that can be applied to the entire cohort to better estimate exposure to specific agents. The enhanced data will improve statistical power and permit identification of the specific agents that are most closely linked with asthma risk. The proposed project has three specific aims. First, we will use cohort data from 1989-2011 to determine the association between occupational exposure and incident asthma. We will evaluate a potential healthy worker effect by taking into account job changes in relation to asthma status. Second, we will perform a cross-sectional study (2013) to determine the association between occupational exposure and asthma severity/control. Third, we will conduct a prospective study to determine the association between occupational exposure and incident asthma (2007-2013, n~1,800 cases). In summary, this project will, for the first time, determine the relation of a common occupational exposure among nurses to risk of adult-onset asthma and poor asthma control. The project provides a unique opportunity, in a large occupational cohort, to test several novel hypotheses about occupational exposures to disinfectant or cleaning agents and their impact on asthma. The study results could have a major public health impact on the well-being of health care workers, cleaners, and others who are regularly exposed to disinfectant or cleaning agents.